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Method for determining surivival prognosis of patients suffering from non-small cell lung cancer (NSCLC)

a prognosis technology, applied in the field of determining the survival prognosis of patients suffering from non-small cell lung cancer, can solve the problems of short survival time after resection, poor prognosis of most types of lung cancer, and only side effects of follow-up treatment, so as to achieve the effect of determining the survival prognosis

Inactive Publication Date: 2013-01-17
PAMGENE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides methods and devices for determining the survival prognosis of patients with non-small cell lung cancer by measuring the kinase activity of a sample obtained from the tumor. The method involves measuring phosphorylation levels in the presence and absence of a protein kinase inhibitor to determine the differential phosphorylation level that indicates the patient's survival prognosis. This information can be used to predict the response of the patient to a medicament and to provide personalized treatment options. The invention also relates to an array for carrying out the method and a method for determining the survival prognosis of a patient by measuring phosphorylation levels of phosphorylation sites present in peptide markers.

Problems solved by technology

It is generally known that most types of lung cancer have a poor prognosis.
The consequence is a short survival time after resection.
For this group of patients, follow up treatment brings no benefit but only the side effects associated with the treatment.
Side effects of chemotherapy are severe and also a rather mild therapy like treatment with gefitinib can have very unpleasant side effects.
Therefore, it is no option to subject all persons diagnosed with lung cancer to adjuvant therapy after surgery.

Method used

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  • Method for determining surivival prognosis of patients suffering from non-small cell lung cancer (NSCLC)

Examples

Experimental program
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example 1

Example Showing Measurements of Kinase Activity of NSCLC Tumor Tissue in the Presence and in the Absence of the Protein Kinase Inhibitor Gefitinib

[0103]The method of the present invention allows the measurement of the kinase activity in lysates prepared from fresh frozen NSCLC tumor tissue.

[0104]The inventors have surprisingly found that the survival prognosis can be classified by testing inhibition of kinase activity by studying kinase phosphorylation activity and inhibition levels in resection tissue from a tumor. The tumor content for each of the samples was higher than 70%, based on HE staining. 6 samples were taken from patients having a short survival (less than 9 months), 8 samples were taken from patients with a long survival period (over 95 months).

[0105]6 coupes of 10 μm thickness from tumor tissue were lysed in 100 microliter Mammalian Extraction Buffer (M-PER) containing phosphatase and protease inhibitors. After 30 minutes of lysis on ice, and centrifugation for 15 min ...

example 2

Example Showing the Survival Prognosis of NSCLC Patients

[0108]Tumor samples obtained from 2 classes of patients: short term survivors (6 samples) and long term survivors (8 samples) were incubated as described in example 1 on PamChip® arrays. The fluorescence from the spots in the images was quantified for quantitative purposes.

[0109]For each peptide the ratio of inhibited versus not inhibited signal was calculated and a one way ANOVA was performed to identify peptides with a significant difference between the long and short term survivors. Table 1 enlists 19 out of the 140 peptides that have a probability (p) for equal means over the 2 patient classes of p <0.01. A heatmap showing the ratio of inhibited versus not inhibited phosphorylation signal in each of the peptide markers listed in Table 1, is provided in FIG. 1. Whereas the dotted squares indicate a positive ratio and the non-dotted squares a negative ratio, the grey intensity of the squares is proportional to the ratio level...

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Abstract

The present invention relates to a method for determining the survival prognosis of patients suffering from non-small cell lung cancer. More specifically, the present invention provides methods which measure kinase activity by studying phosphorylation levels in response to a kinase inhibitor and profiles in samples obtained from patients diagnosed with non-small cell lung cancer. The present invention also provides methods for predicting the response of a patient diagnosed with non-small cell lung cancer to a medicament.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a method for determining the survival prognosis of patients suffering from non-small cell lung cancer. More specifically, the present invention provides methods which measure kinase activity by studying phosphorylation levels and profiles in samples obtained from patients diagnosed with non-small cell lung cancer.BACKGROUND OF THE INVENTION[0002]At present lung cancer is considered to be one of the most important causes of death, especially in adults at the ages from 50 to 69 years old. Long term exposure to smoking is the cause of lung cancer for 90% of the cases. Among male smokers, the lifetime risk of developing lung cancer is about 17%; among female smokers the risk is about 11%. For non-smokers, the risk of developing lung cancer is about 1%. The main causes for lung cancer in non-smokers are genetic factors, radon gas, asbestos, air pollution and passive smoking. There are two main types of lung cancer: non-small ce...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C40B30/04
CPCG01N33/57423C12Q1/485
Inventor DE WIJN, RICHARDRUIJTENBEEK, ROBBYHILHORST, MARIA HELENA
Owner PAMGENE
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